Species

calcium channels

Summary

Summary: Voltage-dependent cell membrane glycoproteins selectively permeable to calcium ions. They are categorized as L-, T-, N-, P-, Q-, and R-types based on the activation and inactivation kinetics, ion specificity, and sensitivity to drugs and toxins. The L- and T-types are present throughout the cardiovascular and central nervous systems and the N-, P-, Q-, & R-types are located in neuronal tissue.

Top Publications

The capsaicin receptor: a heat-activated ion channel in the pain pathway

..We propose that STIM1, a ubiquitously expressed protein that is conserved from Drosophila to mammalian cells, plays an essential role in SOC influx and may be a common component of SOC and CRAC channels...

Store-operated calcium channels

Anant B ParekhDepartment of Physiology, University of Oxford, United KingdomPhysiol Rev 85:757-810. 2005

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A forty-kilodalton protein of the inner membrane is the mitochondrial calcium uniporter

..Although overexpression of CRACM1 did not affect CRAC currents, RNAi-mediated knockdown disrupted its activation. CRACM1 could be the CRAC channel itself, a subunit of it, or a component of the CRAC signaling machinery...

..The channel is inwardly rectifying, making it especially effective for Ca2+ uptake into energized mitochondria. Thus, we conclude that the properties of the current mediated by this novel channel are those of the MCU...

Chan Young ParkDepartment of Neurobiology, Stanford University School of Medicine, CA 94305, USACell 136:876-90. 2009

..These studies establish a molecular mechanism for store-operated Ca(2+) entry in which the direct binding of STIM1 to Orai1 drives the accumulation and the activation of CRAC channels at ER-PM junctions...

The family of voltage-gated calcium channels serves as the key transducers of cell surface membrane potential changes into local intracellular calcium transients that initiate many different physiological events...

..This article presents the molecular relationships and physiological functions of these Ca(2+) channel proteins and provides information on their molecular, genetic, physiological, and pharmacological properties...

..NAADP) is a widespread and potent calcium-mobilizing messenger that is highly unusual in activating calcium channels located on acidic stores. However, the molecular identity of the target protein is unclear...

..The emergence of complex decoding properties from the juxtaposition of common elements, and the techniques developed herein, promise generalization to numerous molecules residing near Ca(2+) sources...

..We conclude that the human Orai1 and Orai3 channels undergo a dimer-to-tetramer transition to form a Ca(2+)-selective pore during store-operated activation and that Orai3 forms a dimeric nonselective cation pore upon activation by 2-APB...

..By contrast, TPCN2-specific Ca(2+)-release is unaffected by emptying ER-based Ca(2+) stores. In conclusion, these findings indicate that TPCN2 is a major component of the long-sought lysosomal NAADP-dependent Ca(2+)-release channel...

..Thus different plant genera, including Allium and Brassica, have developed evolutionary convergent strategies that target TRPA1 channels on sensory nerve endings to achieve chemical deterrence...

Calcium channel regulation and presynaptic plasticity

William A CatterallDepartment of Pharmacology, University of Washington, Seattle, WA 98195 7280, USANeuron 59:882-901. 2008

..We propose that presynaptic Ca(2+) channels serve as the regulatory node in a dynamic, multilayered signaling network that exerts short-term control of neurotransmission in response to synaptic activity...

CRACM1 (also called Orai1) constitutes the pore subunit of store-operated calcium release-activated calcium channels. A point mutation in the gene encoding CRACM1 is associated with severe combined immunodeficiency disease in humans...

..These findings suggest that the organellar membrane potential may undergo large regulatory changes and may explain the specificity of PI(3,5)P(2) in regulating the fusogenic potential of intracellular organelles...

..Thus, ERp44 senses the environment in the ER lumen and modulates IP(3)R1 activity accordingly, which should in turn contribute to regulating both intralumenal conditions and the complex patterns of cytosolic Ca(2+) concentrations...

..Orai1 and the associated calcium release-activated calcium (CRAC) channel were discovered in the immune system. Existence also in endothelial cells has been suggested, but the relevance to endothelial biology is mostly unknown...

..The inability of cryptococcal cells that lacked the Cch1-Mid1 channel to survive ER stress suggests that Cch1 and its co-regulator, Mid1, are critical players in the restoration of Ca(2+) homeostasis...

Youjun WangDepartment of Biochemistry and Cardiovascular Research Center, Temple University School of Medicine, 3400 North Broad Street, Philadelphia, PA 19140, USAScience 330:105-9. 2010

..2 and Orai1 channels. Hence, STIM1 interacts with and reciprocally controls two major calcium channels hitherto thought to operate independently. Such coordinated control of the widely expressed Ca(V)1...

..In contrast to the more common view of the TRP family as comprising store-operated channels, we propose that many TRPC heteromers form diverse receptor-regulated nonselective cation channels in the mammalian brain...

..attenuates the calcium responses to hypoxia and subsequent AMPK phosphorylation, while inhibition of L-type calcium channels has no effect...

Cigarette smoke-induced neurogenic inflammation is mediated by alpha,beta-unsaturated aldehydes and the TRPA1 receptor in rodents

Eunice AndreCenter of Excellence for the Study of Inflammation, University of Ferrara, Ferrara, ItalyJ Clin Invest 118:2574-82. 2008

..These data identify alpha,beta-unsaturated aldehydes as the main causative agents in CS that via TRPA1 stimulation mediate airway neurogenic inflammation and suggest a role for TRPA1 in the pathogenesis of CS-induced diseases...

..3(-/-) mouse. We propose a specific role for Ca(V)2.3 Ca(2+) channels in second-phase insulin release, that of mediating the Ca(2+) entry needed for replenishment of the releasable pool of granules as well as islet cell differentiation...

Research Grants71

..on the cerebellar disorders arising from mutations of the genes that specify the structure of neuronal calcium channels, because: 1) Such "channelopathy" diseases form one of the largest groups of heritable, degenerative, ..

..and bipolar disorder medication that decreases glutamate release through interactions with sodium and calcium channels. We conducted both open-label and placebo-controlled trials of lamotrigine in corticosteroid-treated patients ..

..This will allow us to test the effects of specific proteins on nerve cell dysfunction and cell death in live animals with the ultimate goal of identifying new therapeutic avenues for treatment of human neurodegenerative diseases. ..

..function in amyloidogenesis associated with Alzheimer's disease, 2) investigate the role of TRPC calcium channels and dysregulation of calcium homeostasis in dopaminergic neuronal cell death associated with Parkinson[..

..This combination of intensive research, mentoring, and formal education will provide the necessary background for me to become a successful, independent researcher in obstetric pharmacoepidemiology. ..

..This project explores the underlying cardiovascular physiology of patients with HFpEF with the goal of identifying new therapeutic targets that would allow improved treatment of this devastating disease. ..

..These studies will increase understanding of regulation of the heart by the sympathetic nervous system and give essential new insight into the molecular and functional changes in the Cav1.2 signaling complex in heart failure. ..

..1) To confirm the importance of astrocyte-derived TSP- 1/TSP-2 signaling through neuronal a2d-1 voltage-gated calcium channels in mediating the reversible paralysis of relapsing EAE by acting on excitatory synapses in motor pathways of ..

..A major source of calcium entry into these cells is through voltage-dependent L-type calcium channels. The general goal of this proposal is to investigate the poorly understood mechanisms controlling calcium ..

..The data and techniques in these studies will form the basis of my independent research program on viral calcium channels and development of viroporin inhibitors as tools for molecular virology studies and leads for antiviral drug ..

..The second goal is to investigate immunosuppression mediated by blockade of specific ion channels in T lymphocytes - a potassium channel Kv1.3 and a calcium channel Orai1 - for treatment of autoimmune disorders. ..

..Impact: This research program will reveal how retinoschisin interacts with its binding partners, specifically L-VGCCs and PMCA1, and new roles of retinoschisin in photoreceptor physiology and function. ..

..e., blood pressure control), and morbidity and mortality (i.e., hospitalization and death due to cardiovascular and cerebrovascular disease). Such studies are consistent with NIA's priority comparative effectiveness research area. ..

..3) What is the role of G[unreadable][unreadable] binding the synaptic vesicle proteins or voltage-dependent calcium channels in presynaptic terminals in NMDAR- versus mGluR-dependent LTD? There is a probable role for LTD in memory ..

..Better understanding of TSP, a2d-1, hevin and SPARC may lead to improvements in the treatment of neurological diseases such as schizophrenia and autism which are characterized by aberrant synaptic connectivity. ..

..Completion of this study will allow us to expand the scope of the parent proposal and accelerate the tempo of scientific research in this under investigated field and the discovery of new drug targets for chronic pain disorders. ..

..The findings will provide genomic and molecular insights into regulation of the expression of L-type calcium channels that play a critical role in excitation-contraction coupling in the normal state and during inflammation...

..Results obtained by these experiments will improve the knowledge of hypercalciuria, a significant risk factor for kidney stones, and may contribute to the development of novel treatment strategies in nephrolithiasis. ..

..This information will also be valuable to the pharmacologist by providing insight into possible mechanisms responsible for alterations due to differences in the route of administration and to drug interactions...

..This study should significantly enhance current knowledge with respect to Ca2+signaling and constriction of cerebral arteries in health and disease and provide insight into possible new therapies for the treatment of cerebral vasospasm. ..

..Specifically, we wish to accomplish the following: 1) to characterize voltage-dependent calcium channels and study their influence on the intracellular calcium ion concentration and insulin release; 2) to study ..

..This form of LTP is induced by 200 Hz stimulation through voltage dependent calcium channels, and contributes to the LTP observed in typical in vitro and in vivo experiments (i.e. 100 Hz stimulation)...